HTLV-1-induced leukotriene B4 secretion by T cells promotes T cell recruitment and virus propagation

  • Nat Commun. 2017 Jun 22;8:15890. doi: 10.1038/ncomms15890.
Florent Percher  1  2  3 ,  Céline Curis  1  2  3 ,  Eléonore Pérès  4 ,  Maria Artesi  5 ,  Nicolas Rosewick  5  6 ,  Patricia Jeannin  1  2 ,  Antoine Gessain  1  2 ,  Olivier Gout  7 ,  Renaud Mahieux  8 ,  Pierre-Emmanuel Ceccaldi  1  2  3 ,  Anne Van den Broeke  5  6 ,  Madeleine Duc Dodon  4 ,  Philippe V Afonso  1  2
Affiliations
  • 1. Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Département de Virologie, Institut Pasteur, Paris F-75015, France.
  • 2. Centre National de la Recherche Scientifique (CNRS) UMR 3569, Paris F-75015, France.
  • 3. Université Paris Diderot, Sorbonne Paris Cité, Paris F-75013, France.
  • 4. Laboratoire de Biologie et Modélisation de la Cellule, ENS de Lyon, INSERM U1210 CNRS-UCBL UMR 5239, UMS 3444 SFR Biosciences-Lyon, Lyon F-69007, France.
  • 5. Unit of Animal Genomics, Groupe Interdisciplinaire Génoprotéomique Appliquée (GIGA), Université de Liège, Liège B-4000, Belgium.
  • 6. Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels B-1000, Belgium.
  • 7. Service de Neurologie, Fondation Ophtalmologique Adolphe de Rothschild, Paris F-75019, France.
  • 8. Equipe Oncogenèse Rétrovirale, ENS de Lyon, and Equipe Labélisée Ligue Nationale Contre le Cancer, Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR 5308, Lyon F-69007, France.
PMID: 28639618 DOI: 10.1038/ncomms15890
Abstract

The human T-lymphotropic virus type 1 (HTLV-1) is efficiently transmitted through cellular contacts. While the molecular mechanisms of viral cell-to-cell propagation have been extensively studied in vitro, those facilitating the encounter between infected and target cells remain unknown. In this study, we demonstrate that HTLV-1-infected CD4 T cells secrete a potent chemoattractant, leukotriene B4 (LTB4). LTB4 secretion is dependent on Tax-induced transactivation of the pla2g4c gene, which encodes the cytosolic Phospholipase A2 gamma. Inhibition of LTB4 secretion or LTB4 receptor knockdown on target cells reduces T-cell recruitment, cellular contact formation and virus propagation in vitro. Finally, blocking the synthesis of LTB4 in a humanized mouse model of HTLV-1 Infection significantly reduces proviral load. This results from a decrease in the number of infected clones while their expansion is not impaired. This study shows the critical role of LTB4 secretion in HTLV-1 transmission both in vitro and in vivo.